CN104334535B - 用于治疗干眼和其他粘膜疾病的具有钠通道阻断活性的树状聚体样氨基酰胺 - Google Patents

用于治疗干眼和其他粘膜疾病的具有钠通道阻断活性的树状聚体样氨基酰胺 Download PDF

Info

Publication number
CN104334535B
CN104334535B CN201380028574.3A CN201380028574A CN104334535B CN 104334535 B CN104334535 B CN 104334535B CN 201380028574 A CN201380028574 A CN 201380028574A CN 104334535 B CN104334535 B CN 104334535B
Authority
CN
China
Prior art keywords
compound
treatment
independently
disease
formula
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN201380028574.3A
Other languages
English (en)
Chinese (zh)
Other versions
CN104334535A (zh
Inventor
迈克尔·罗斯·约翰逊
威廉·罗伯特·特林
理查德·C·博谢
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Parion Sciences Inc
Original Assignee
Parion Sciences Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Parion Sciences Inc filed Critical Parion Sciences Inc
Publication of CN104334535A publication Critical patent/CN104334535A/zh
Application granted granted Critical
Publication of CN104334535B publication Critical patent/CN104334535B/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
    • C07D241/28—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
    • C07D241/30—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms in which said hetero-bound carbon atoms are part of a substructure —C(=X)—X—C(=X)—X— in which X is an oxygen or sulphur atom or an imino radical, e.g. imidoylguanidines
    • C07D241/32—(Amino-pyrazinoyl) guanidines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965—Non-condensed pyrazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/16—Central respiratory analeptics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/16—Emollients or protectives, e.g. against radiation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/04—Artificial tears; Irrigation solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
    • C07D241/28—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
    • C07D241/34—(Amino-pyrazine carbonamido) guanidines

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Pulmonology (AREA)
  • Toxicology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Otolaryngology (AREA)
  • Reproductive Health (AREA)
  • Endocrinology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Peptides Or Proteins (AREA)
CN201380028574.3A 2012-05-29 2013-05-29 用于治疗干眼和其他粘膜疾病的具有钠通道阻断活性的树状聚体样氨基酰胺 Expired - Fee Related CN104334535B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201261652481P 2012-05-29 2012-05-29
US61/652,481 2012-05-29
PCT/US2013/043080 WO2013181232A2 (fr) 2012-05-29 2013-05-29 Amino-amides de type dendrimères possédant une activité de blocage des canaux sodiques pour le traitement de la sécheresse oculaire et d'autres maladies des muqueuses

Publications (2)

Publication Number Publication Date
CN104334535A CN104334535A (zh) 2015-02-04
CN104334535B true CN104334535B (zh) 2016-10-05

Family

ID=49671001

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201380028574.3A Expired - Fee Related CN104334535B (zh) 2012-05-29 2013-05-29 用于治疗干眼和其他粘膜疾病的具有钠通道阻断活性的树状聚体样氨基酰胺

Country Status (24)

Country Link
US (4) US8980898B2 (fr)
EP (2) EP3366680B1 (fr)
JP (3) JP6272312B2 (fr)
KR (1) KR102109223B1 (fr)
CN (1) CN104334535B (fr)
AU (2) AU2013267504B2 (fr)
BR (1) BR112014029329A2 (fr)
CA (1) CA2872029A1 (fr)
CY (1) CY1120397T1 (fr)
DK (1) DK2855435T3 (fr)
EA (2) EA032734B1 (fr)
ES (1) ES2675588T3 (fr)
HK (1) HK1204276A1 (fr)
HU (1) HUE039734T2 (fr)
LT (1) LT2855435T (fr)
MX (1) MX2014014648A (fr)
MY (1) MY171122A (fr)
PH (1) PH12014502624B1 (fr)
PL (1) PL2855435T3 (fr)
PT (1) PT2855435T (fr)
SG (1) SG11201407867VA (fr)
SI (1) SI2855435T1 (fr)
TR (1) TR201809148T4 (fr)
WO (1) WO2013181232A2 (fr)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6858615B2 (en) 2002-02-19 2005-02-22 Parion Sciences, Inc. Phenyl guanidine sodium channel blockers
PT2276493T (pt) 2008-04-18 2019-01-10 Reata Pharmaceuticals Inc Moduladores de inflamação anti-oxidantes: derivados de ácidos oleonucleicos com uma modificação no grupo aminno e outras modificações em c-17
PT2723176T (pt) 2011-06-27 2017-07-18 Parion Sciences Inc Dipéptido química e metabolicamente estável que possui potente atividade bloqueadora do canal de sódio
AR086745A1 (es) 2011-06-27 2014-01-22 Parion Sciences Inc 3,5-diamino-6-cloro-n-(n-(4-(4-(2-(hexil(2,3,4,5,6-pentahidroxihexil)amino)etoxi)fenil)butil)carbamimidoil)pirazina-2-carboxamida
JP6272312B2 (ja) 2012-05-29 2018-01-31 パリオン・サイエンシィズ・インコーポレーテッド ドライアイおよび他の粘膜疾患の治療のためのナトリウムチャネル遮断活性を有するデンドリマー様アミノアミド
CA2882418C (fr) 2012-09-10 2021-05-04 Reata Pharmaceuticals, Inc. Derives c17-alcanediyles et alcenediyles de l'acide oleanolique et leurs procedes d'utilisation
EP2931712B8 (fr) 2012-12-17 2018-05-23 Parion Sciences, Inc. Composés 3,5-diamino-6-chloro-n-(n-(4-phénylbutyl)carbaminidoyl) pyrazin-2-carboxamidiques
AP2015008556A0 (en) 2012-12-17 2015-06-30 Parion Sciences Inc Chloro-pyrazine carboxamide derivatives useful forthe treatment of diseases favoured by insufficien t mucosal hydration
CA2922162A1 (fr) 2013-08-23 2015-02-26 Parion Sciences, Inc. Agents mucolytiques au dithiol
US9102633B2 (en) 2013-12-13 2015-08-11 Parion Sciences, Inc. Arylalkyl- and aryloxyalkyl-substituted epithelial sodium channel blocking compounds
US20150376145A1 (en) 2014-06-30 2015-12-31 Parion Sciences, Inc. Stable sodium channel blockers
WO2016123335A1 (fr) 2015-01-30 2016-08-04 Parion Sciences, Inc. Nouveaux agents mucolytiques au monothiol
WO2016133967A2 (fr) * 2015-02-18 2016-08-25 Parion Sciences, Inc. Bloqueurs de canaux sodiques pour le traitement de troubles de la peau
CN107708680A (zh) 2015-04-30 2018-02-16 帕里昂科学公司 新的二硫醇粘液溶解剂的前药
GB201610854D0 (en) 2016-06-21 2016-08-03 Entpr Therapeutics Ltd Compounds
GB201619694D0 (en) 2016-11-22 2017-01-04 Entpr Therapeutics Ltd Compounds
GB201717051D0 (en) 2017-10-17 2017-11-29 Enterprise Therapeutics Ltd Compounds
CN109752354A (zh) * 2017-11-06 2019-05-14 锐准医光股份有限公司 整合米洛光学干涉显微术与荧光显微术的光学切层装置
GB201808093D0 (en) 2018-05-18 2018-07-04 Enterprise Therapeutics Ltd Compounds
CN109160888B (zh) * 2018-10-09 2022-03-01 四川医立特生物医药有限公司 一种含脒基的对称化合物及其应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007146867A2 (fr) * 2006-06-09 2007-12-21 Parion Sciences Inc. Bloqueurs de canaux sodiques pyrazinoylguanidine aliphatiques dotés d'une activité agoniste bêta
WO2008030217A2 (fr) * 2005-07-25 2008-03-13 Parion Sciences, Inc. Procédés de réduction du risque d'infection par des pathogènes avec des bloquants amide soluble et ester pyrazinoylguanidine du canal sodium
WO2008124491A1 (fr) * 2007-04-03 2008-10-16 Parion Sciences, Inc. Composes de pyrazinoylguanidine destines a etre utilises en tant que modulateurs de gout
CN101534813A (zh) * 2006-09-07 2009-09-16 帕里昂科学公司 通过使用钠通道阻断剂和渗透调节剂的治疗来增加粘膜水化和粘液清除的方法
CN101951913A (zh) * 2008-02-26 2011-01-19 帕里昂科学公司 聚芳族钠通道阻断剂

Family Cites Families (101)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE639386A (fr) 1962-10-30
US3361306A (en) 1966-03-31 1968-01-02 Merck & Co Inc Aerosol unit dispensing uniform amounts of a medically active ingredient
US3565070A (en) 1969-02-28 1971-02-23 Riker Laboratories Inc Inhalation actuable aerosol dispenser
US4312860A (en) 1980-10-24 1982-01-26 Regents Of The University Of California Lung surfactant compositions
US4479932A (en) 1982-05-18 1984-10-30 University Of Florida Brain-specific drug delivery
US4540564A (en) 1982-05-18 1985-09-10 University Of Florida Brain-specific drug delivery
US4805811A (en) 1985-03-29 1989-02-21 Aktiebolaget Draco Dosage device
US5385938B1 (en) * 1986-12-23 1997-07-15 Tristrata Inc Method of using glycolic acid for treating wrinkles
US5100806A (en) 1989-03-24 1992-03-31 Macri James N Method for detecting Edwards syndrome
US4955371A (en) 1989-05-08 1990-09-11 Transtech Scientific, Inc. Disposable inhalation activated, aerosol device for pulmonary medicine
CA2063273C (fr) 1989-07-11 2002-09-24 Bradley J. Benson Surfactants pulmonaires et methodes
DE4003272A1 (de) 1990-02-03 1991-08-08 Boehringer Ingelheim Kg Neue treibgasmischungen und ihre verwendung in arzneimittelzubereitungen
US5614216A (en) 1990-10-17 1997-03-25 The Liposome Company, Inc. Synthetic lung surfactant
US5292498A (en) 1991-06-19 1994-03-08 The University Of North Carolina At Chapel Hill Method of treating lung disease with uridine triphosphates
CA2444415A1 (fr) 1991-07-02 1993-01-21 Nektar Therapeutics Methode et instrument pour la delivrance de medicaments en aerosol
DE69218455T2 (de) 1991-12-18 1997-10-23 Minnesota Mining And Mfg. Co., Saint Paul, Minn. Aerosolzusammensetzungen für arzneimittelsuspensionen
US7105152B1 (en) 1991-12-18 2006-09-12 3M Innovative Properties Company Suspension aerosol formulations
US5261538A (en) 1992-04-21 1993-11-16 Glaxo Inc. Aerosol testing method
AUPM411494A0 (en) 1994-02-25 1994-03-24 Central Sydney Area Health Service Method and device for the provocation of upper or lower airway narrowing and/or the induction of sputum
US5522385A (en) 1994-09-27 1996-06-04 Aradigm Corporation Dynamic particle size control for aerosolized drug delivery
US5622163A (en) 1994-11-29 1997-04-22 Iep Group, Inc. Counter for fluid dispensers
US5544647A (en) 1994-11-29 1996-08-13 Iep Group, Inc. Metered dose inhalator
US5656256A (en) 1994-12-14 1997-08-12 The University Of North Carolina At Chapel Hill Methods of treating lung disease by an aerosol containing benzamil or phenamil
CZ296256B6 (cs) 1995-04-14 2006-02-15 Glaxo Wellcome Inc. Inhalátor a inhalacní systém
CN1262556C (zh) 1997-02-06 2006-07-05 印斯拜尔药品股份有限公司 特定的二核苷酸和它们作为粘膜纤毛清除和纤毛颤动频率调节剂的应用
US7223744B2 (en) 1997-02-10 2007-05-29 Inspire Pharmaceuticals, Inc. Pharmaceutical formulation comprising dinucleoside polyphosphates and salts thereof
US6818629B2 (en) 1997-02-10 2004-11-16 Inspire Pharmaceuticals, Inc. Pharmaceutical formulation comprising P1-(2'-deoxycytidine 5'-)P4-(uridine 5'-) tetraphosphate
US20010031244A1 (en) 1997-06-13 2001-10-18 Chiesi Farmaceutici S.P.A. Pharmaceutical aerosol composition
GB9807232D0 (en) 1998-04-03 1998-06-03 Univ Cardiff Aerosol composition
US7105552B2 (en) 1998-05-08 2006-09-12 Theracos, Inc. Heterocyclic analogs of diphenylethylene compounds
JP2002527459A (ja) 1998-10-20 2002-08-27 ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル 粘膜表面を水和する方法
US6926911B1 (en) 1998-12-22 2005-08-09 The University Of North Carolina At Chapel Hill Compounds and methods for the treatment of airway diseases and for the delivery of airway drugs
US6329034B1 (en) 1999-01-18 2001-12-11 Roger L. Pendry Label having tab member and methods for forming, applying and using the same
US6116234A (en) 1999-02-01 2000-09-12 Iep Pharmaceutical Devices Inc. Metered dose inhaler agitator
JP4540906B2 (ja) 1999-06-05 2010-09-08 イノバータ・バイオメッド・リミテッド 放出システム
GB2353222B (en) 1999-06-23 2001-09-19 Cambridge Consultants Inhalers
GB9920839D0 (en) 1999-09-04 1999-11-10 Innovata Biomed Ltd Inhaler
AU1068401A (en) 1999-10-12 2001-04-23 Shl Medical Ab Inhaler
TWI310688B (en) 1999-10-29 2009-06-11 Nektar Therapeutics Dry powder compositions having improved dispersivity
GB9928265D0 (en) 1999-12-01 2000-01-26 Innovata Biomed Ltd Inhaler
SE9904706D0 (sv) 1999-12-21 1999-12-21 Astra Ab An inhalation device
US7345051B2 (en) 2000-01-31 2008-03-18 Genaera Corporation Mucin synthesis inhibitors
US7171965B2 (en) 2000-02-01 2007-02-06 Valois S.A.S. Breath actuated dry powder inhaler and tape dose strip
FR2813593B1 (fr) 2000-09-07 2002-12-06 Valois Sa Dispositif de distribution de produit fluide de type multidose
GB0026647D0 (en) 2000-10-31 2000-12-13 Glaxo Group Ltd Medicament dispenser
US6858615B2 (en) 2002-02-19 2005-02-22 Parion Sciences, Inc. Phenyl guanidine sodium channel blockers
US6858614B2 (en) 2002-02-19 2005-02-22 Parion Sciences, Inc. Phenolic guanidine sodium channel blockers
US6889690B2 (en) 2002-05-10 2005-05-10 Oriel Therapeutics, Inc. Dry powder inhalers, related blister devices, and associated methods of dispensing dry powder substances and fabricating blister packages
EP1542667B1 (fr) 2002-07-24 2012-03-07 PTC Therapeutics, Inc. Composes d'acide benzoique a substitution ureido et leur utilisation pour la suppression de non-sens et le traitement de maladie
US6903105B2 (en) 2003-02-19 2005-06-07 Parion Sciences, Inc. Sodium channel blockers
ES2528195T3 (es) 2003-04-11 2015-02-05 Ptc Therapeutics, Inc. Compuestos de ácido 1,2,4-oxadiazol benzoico y su uso para la supresión sin sentido y el tratamiento de enfermedades
EP1488819A1 (fr) 2003-06-16 2004-12-22 Rijksuniversiteit te Groningen Inhalateur de poudre sèche et procédé d'inhalation pulmonaire de poudre sèche
JP2007502827A (ja) 2003-08-18 2007-02-15 パリオン・サイエンシィズ・インコーポレーテッド 脂肪族ピラジノイルグアニジンナトリウムチャネルブロッカー
JP4805824B2 (ja) 2003-08-18 2011-11-02 パリオン・サイエンシィズ・インコーポレーテッド キャップ化ピラジノイルグアニジンナトリウムチャネルブロッカー
WO2005016879A2 (fr) 2003-08-18 2005-02-24 Parion Sciences, Inc. Bloqueurs du canal sodique a pyrazinoyl-guanidine cyclique
US20050090505A1 (en) 2003-08-18 2005-04-28 Johnson Michael R. Methods of reducing risk of infection from pathogens
US7745442B2 (en) 2003-08-20 2010-06-29 Parion Sciences, Inc. Methods of reducing risk of infection from pathogens
US20090253714A1 (en) 2003-08-20 2009-10-08 Johnson Michael R Methods of reducing risk of infection from pathogens
US7499570B2 (en) 2004-03-02 2009-03-03 Siemens Corporate Research, Inc. Illumination invariant change detection
US8354427B2 (en) 2004-06-24 2013-01-15 Vertex Pharmaceutical Incorporated Modulators of ATP-binding cassette transporters
US7375102B2 (en) 2004-06-28 2008-05-20 Amgen Sf, Llc Tetrahydroquinazolin-4(3H)-one-related and tetrahydropyrido[2,3-D]pyrimidin-4(3H)-one-related compounds, compositions and methods for their use
KR20070052317A (ko) 2004-08-18 2007-05-21 마이클 알 존슨. 환형 아미드 및 에스테르 피라지노일구아니딘 나트륨 채널차단제
CA2575670A1 (fr) 2004-08-18 2006-03-02 Michael R. Johnson Bloqueurs des canaux sodiques de pyrazinoylguanidine a amide et ester aliphatique
US7399766B2 (en) 2004-08-18 2008-07-15 Parion Sciences, Inc. Soluble amide & ester pyrazinoylguanidine sodium channel blockers
US20090324724A1 (en) 2004-08-18 2009-12-31 Parion Sciences, Inc. Soluble amide & ester pyrazinoylguanidine sodium channel blockers
EP2301536B1 (fr) 2004-10-13 2014-04-09 PTC Therapeutics, Inc. Composes de suppression de non-sens et procedes de leur utilisation
JP2009221164A (ja) 2008-03-17 2009-10-01 Nitto Denko Corp 肺線維症処置剤
ATE551421T1 (de) 2005-01-07 2012-04-15 Alnylam Pharmaceuticals Inc Rnai modulation von rsv und deren therapeutische verwendungen
US7588817B2 (en) 2005-03-11 2009-09-15 Jds Uniphase Corporation Engraved optically variable image device
US7807834B2 (en) 2005-08-03 2010-10-05 Parion Sciences, Inc. Capped pyrazinoylguanidine sodium channel blockers
WO2007065437A2 (fr) 2005-12-06 2007-06-14 P2-Science Aps Modulation de la voie des recepteurs p2y2
AU2006331565A1 (en) 2005-12-27 2007-07-05 Vertex Pharmaceuticals Incorporated Compounds useful in CFTR assays and methods therewith
EP1981483A1 (fr) 2006-01-24 2008-10-22 Nexbio, Inc. Technologie pour la preparation de microspheres macromoleculaires
US7645789B2 (en) 2006-04-07 2010-01-12 Vertex Pharmaceuticals Incorporated Indole derivatives as CFTR modulators
AU2007249269A1 (en) 2006-05-12 2007-11-22 Vertex Pharmaceuticals Incorporated Compositions of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl)-1,4-dihydro-4-oxoquinoline-3-carboxamide
TWI334164B (en) 2006-06-07 2010-12-01 Ind Tech Res Inst Method of manufacturing nitride semiconductor substrate and composite material substrate
US20110195973A1 (en) 2006-06-09 2011-08-11 Parion Sciences, Inc. Cyclic substituted pyrazinoylguanidine sodium channel blockers possessing beta agonist activity
AU2007257781B2 (en) 2006-06-09 2012-11-22 Parion Sciences, Inc. Phenyl substituted pyrazinoylguanidine sodium channel blockers possessing beta agonist activity
US8058278B2 (en) 2006-09-07 2011-11-15 Parion Sciences, Inc. Methods of enhancing mucosal hydration and mucosal clearance by treatment with sodium channel blockers and osmolytes
US7981898B2 (en) 2006-09-07 2011-07-19 Parion Sciences, Inc. Methods of enhancing mucosal hydration and mucosal clearance by treatment with sodium channel blockers and osmolytes
US8563573B2 (en) 2007-11-02 2013-10-22 Vertex Pharmaceuticals Incorporated Azaindole derivatives as CFTR modulators
US7754739B2 (en) 2007-05-09 2010-07-13 Vertex Pharmaceuticals Incorporated Modulators of CFTR
US20080293740A1 (en) 2007-04-03 2008-11-27 Parion Sciences, Inc. Method of treating acid-sensing ion channel mediated pain, cough suppression, and central nervous system disorders
US20100215588A1 (en) 2007-04-26 2010-08-26 Rami Skaliter Therapeutic delivery of inhibitory nucleic acid molecules to the respiratory system
EP1997502A1 (fr) 2007-06-01 2008-12-03 CHIESI FARMACEUTICI S.p.A. Agents tensioactifs reconstitués dotés de propriétés améliorées
DK2011907T3 (da) 2007-07-02 2010-05-17 Centre Nat Rech Scient Fremgangsmåde til fremstilling af hydrogengas og carbon-nanorør ud fra en katalytisk nedbrydning af ethanol
US8131579B2 (en) 2007-07-09 2012-03-06 Raytheon Company Web-based system and application for collaborative planning of a networked program schedule
AU2008279129A1 (en) 2007-07-24 2009-01-29 Nexbio, Inc. Technology for the preparation of microparticles
AU2008310734B2 (en) 2007-10-10 2014-06-05 Parion Sciences, Inc. Delivering osmolytes by nasal cannula
EP2217249A4 (fr) 2007-11-06 2011-10-12 Benaroya Res Inst Inhibition de versicane par de l'arnsi et autres molécules
NZ587545A (en) 2008-02-28 2012-09-28 Vertex Pharma Heteroaryl derivatives as cftr modulators
NZ588006A (en) 2008-03-31 2012-08-31 Vertex Pharma Pyridine derivatives as CFTR modulators, in particular N-(6-(benzylamino)-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide
US20100074881A1 (en) 2008-07-11 2010-03-25 Parion Sciences, Inc. Multiple nebulizer systems
CA2741178A1 (fr) 2008-10-23 2010-04-29 Vertex Pharmaceuticals Incorporated Formes solides de n-(4-(7-azadicyclo[2.2.1]heptan-7-yl)-2-(trifluoromethyl)phenyl)-4-oxo-5-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide
US20100316628A1 (en) 2008-12-09 2010-12-16 The General Hospital Corporation Agents and methods for treating respiratory disorders
WO2010078103A1 (fr) 2008-12-30 2010-07-08 Vertex Pharmaceuticals Incorporated Modulateurs du régulateur de la conductance transmembranaire de la fibrose kystique
PT2723176T (pt) 2011-06-27 2017-07-18 Parion Sciences Inc Dipéptido química e metabolicamente estável que possui potente atividade bloqueadora do canal de sódio
AR086745A1 (es) 2011-06-27 2014-01-22 Parion Sciences Inc 3,5-diamino-6-cloro-n-(n-(4-(4-(2-(hexil(2,3,4,5,6-pentahidroxihexil)amino)etoxi)fenil)butil)carbamimidoil)pirazina-2-carboxamida
JP6272312B2 (ja) 2012-05-29 2018-01-31 パリオン・サイエンシィズ・インコーポレーテッド ドライアイおよび他の粘膜疾患の治療のためのナトリウムチャネル遮断活性を有するデンドリマー様アミノアミド
AP2015008556A0 (en) 2012-12-17 2015-06-30 Parion Sciences Inc Chloro-pyrazine carboxamide derivatives useful forthe treatment of diseases favoured by insufficien t mucosal hydration
EP2931712B8 (fr) 2012-12-17 2018-05-23 Parion Sciences, Inc. Composés 3,5-diamino-6-chloro-n-(n-(4-phénylbutyl)carbaminidoyl) pyrazin-2-carboxamidiques

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008030217A2 (fr) * 2005-07-25 2008-03-13 Parion Sciences, Inc. Procédés de réduction du risque d'infection par des pathogènes avec des bloquants amide soluble et ester pyrazinoylguanidine du canal sodium
WO2007146867A2 (fr) * 2006-06-09 2007-12-21 Parion Sciences Inc. Bloqueurs de canaux sodiques pyrazinoylguanidine aliphatiques dotés d'une activité agoniste bêta
CN101534813A (zh) * 2006-09-07 2009-09-16 帕里昂科学公司 通过使用钠通道阻断剂和渗透调节剂的治疗来增加粘膜水化和粘液清除的方法
WO2008124491A1 (fr) * 2007-04-03 2008-10-16 Parion Sciences, Inc. Composes de pyrazinoylguanidine destines a etre utilises en tant que modulateurs de gout
CN101951913A (zh) * 2008-02-26 2011-01-19 帕里昂科学公司 聚芳族钠通道阻断剂

Also Published As

Publication number Publication date
CN104334535A (zh) 2015-02-04
BR112014029329A2 (pt) 2017-06-27
AU2013267504B2 (en) 2017-11-02
EA201491816A1 (ru) 2015-04-30
AU2018200363B2 (en) 2019-10-17
WO2013181232A3 (fr) 2014-01-23
SG11201407867VA (en) 2014-12-30
MX2014014648A (es) 2015-09-04
MY171122A (en) 2019-09-26
KR102109223B1 (ko) 2020-05-11
US8980898B2 (en) 2015-03-17
TR201809148T4 (tr) 2018-07-23
PH12014502624A1 (en) 2015-01-26
US20160122306A1 (en) 2016-05-05
DK2855435T3 (en) 2018-07-16
HK1204276A1 (en) 2015-11-13
EA032734B1 (ru) 2019-07-31
CY1120397T1 (el) 2019-07-10
EP2855435A2 (fr) 2015-04-08
US20150099764A1 (en) 2015-04-09
JP2018058897A (ja) 2018-04-12
ES2675588T3 (es) 2018-07-11
WO2013181232A2 (fr) 2013-12-05
KR20150023302A (ko) 2015-03-05
US20130324559A1 (en) 2013-12-05
EP2855435B1 (fr) 2018-04-11
US20180111907A1 (en) 2018-04-26
PL2855435T3 (pl) 2018-10-31
EP3366680A1 (fr) 2018-08-29
LT2855435T (lt) 2018-09-10
SI2855435T1 (sl) 2018-09-28
EP3366680B1 (fr) 2020-05-13
US10526292B2 (en) 2020-01-07
CA2872029A1 (fr) 2013-12-05
EA201990616A3 (ru) 2019-12-30
JP6272312B2 (ja) 2018-01-31
US9878988B2 (en) 2018-01-30
JP2015518050A (ja) 2015-06-25
AU2013267504A1 (en) 2014-11-06
PT2855435T (pt) 2018-07-03
EA201990616A2 (ru) 2019-07-31
US9260398B2 (en) 2016-02-16
JP2020059732A (ja) 2020-04-16
EP2855435A4 (fr) 2015-12-09
AU2018200363A1 (en) 2018-02-08
PH12014502624B1 (en) 2015-01-26
HUE039734T2 (hu) 2019-01-28

Similar Documents

Publication Publication Date Title
CN104334535B (zh) 用于治疗干眼和其他粘膜疾病的具有钠通道阻断活性的树状聚体样氨基酰胺
US10159672B2 (en) Chemically and metabolically stable dipeptide possessing potent sodium channel blocker activity
CN108033921B (zh) 3,5-二氨基-6-氯-n-(n-(4-(4-(2-(己基(2,3,4,5,6-五羟基己基)氨基)乙氧基)苯基)丁基)甲脒基)吡嗪-2-甲酰胺
KR20060037450A (ko) 사이클릭 피라지노일구아니딘 나트륨 채널 차단제
CN104955812B (zh) 经芳烷基和芳氧基烷基取代的上皮钠通道阻断化合物

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20161005

Termination date: 20200529

CF01 Termination of patent right due to non-payment of annual fee